On the role of calcium ions in the regulation of glycogenolysis in mouse brain cortical slices.
Using mouse brain cortical slices, we investigated the relative roles of cyclic AMP and of calcium ions as the intracellular messengers for the activation of glycogen phosphorylase (EC 2.4.1.1; alpha-1,4-glucan:orthophosphate glucosyltransferase) induced by noradrenaline and by depolarization. Activation of phosphorylase by 100 microM noradrenaline is mediated by beta-adrenergic receptors and does not require the copresence of adenosine. The role of the concomitant small increase in cyclic AMP is questioned. Short-term treatment with EGTA or LaCl3 abolishes the noradrenaline activation of phosphorylase, pointing to a critical role of extracellular calcium. Depolarization by 25 mM K+ or 100 microM veratridine produces a rapid and large (fourfold) activation of phosphorylase. Only veratridine increases the cyclic AMP levels; exogenous adenosine deaminase essentially blocks this cyclic AMP accumulation but not the phosphorylase activation. A half-maximal activation of phosphorylase occurs at about 12 mM K+. Addition of EGTA or LaCl3 reduces the effect of both depolarizations to a slight and transient activation of phosphorylase. These results indicate that activation of glycogen phosphorylase by K+ or veratridine occurs by a cyclic AMP-independent and calcium-dependent mechanism. The calcium dependency of brain phosphorylase kinase renders this kinase the prime target enzyme for regulation of glycogenolysis by calcium ions.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D006005:Phosphorylases / Q000378:metabolism
C028521:lanthanum chloride; D010656:Phenylephrine; D004533:Egtazic Acid; D007811:Lanthanum; D006003:Glycogen; D006005:Phosphorylases; D007545:Isoproterenol; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine